Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Bolgiano, Barbara, Moran, Eilis, Beresford, Nicola J, Gao, Fang, Care, Rory, Desai, Trusha, Nordgren, Ida Karin, Rudd, Timothy R ORCID: 0000-0003-4434-0333, Feavers, Ian M, Bore, Prashant
et al (show 16 more authors) (2021) Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use. PATHOGENS, 10 (8). 928-.

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Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against <i>Neisseria meningitidis</i> serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM<sub>197</sub>), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine's critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide <i>O</i>-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.

Item Type: Article
Uncontrolled Keywords: Neisseria meningitidis, glycoconjugates, meningitis, adjuvant, chromatography, immunogenicity, polysaccharide, serum bactericidal, acetylation, nuclear magnetic resonance spectroscopy
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 23 Dec 2021 08:57
Last Modified: 09 Feb 2024 09:04
DOI: 10.3390/pathogens10080928
Open Access URL: https://doi.org/10.3390/pathogens10080928
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3145945